The stucture and function relationships of streptokinase will be studied using chemical modification and immunochemical approaches. The goals of this proposal are to identify the groups in the surface of streptokinase and "miniplasminogen", to identify the groups essential for the tight binding of the two proteins, and to critically examine the models for the binding activation of plasminogen by streptokinase. For the chemical approaches, the idea is to locate side chains modified on the proteins with trace isotopic labeling of the native conformations. By using two isotopes and comparing the labeling in individual proteins to their complex, it will be possible to identify surface groups and binding groups. The chemical approach is facilitated with the complete amino acid sequence which has been completed recently on our laboratory. The modifications of amino, carboxyl, tyrosyl, trytophenyl and methionyl groups are proposed. The monoclonal and region-specific antibodies will be raised against streptokinase to confirm the findings using chemical modification approaches. Molecular models will be built based on the homology of steptokinase and plasminogen to serine proteases of known crystal structures. These models will be used to examine the results as well as testing the mechanism of streptokinase binding activities.